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Previous Volume 336:912-918 March 27, 1997 Number 13 Next

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ABSTRACT

Background In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics.

Methods From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system.

Results In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs. 40 percent with placebo).

Conclusions In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.

Source Information

From the Divisions of Pulmonary and Critical Care Medicine (G.R.B., A.P.W., B.W.C., B.B.S.), Biostatistics (W.D.D.), and Biomedical Engineering and Computing (S.B.H.), Vanderbilt University Medical Center, Nashville; the Program of Critical Care Medicine, Department of Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, B.C., Canada (J.A.R.); the University of Miami School of Medicine and Department of Veterans Affairs Medical Center, Miami (R.S.); the Department of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans (W.R.S.); the Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle (K.P.S.); the Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, N.C. (W.J.F.); and the Division of Pulmonary Medicine, Methodist Hospital, Indianapolis (P.E.W.).

Address reprint requests to Dr. Bernard at Rm. T-1217, Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232.

Full Text of this Article

Related Letters:

Ibuprofen in Patients with Sepsis
Zimmerli W., Widmer A. F., Bernard G. R., Wheeler A. P., Christman B.
Extract | Full Text  
N Engl J Med 1997; 337:710, Sep 4, 1997. Correspondence

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